19-40764993-GTCGTTC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004596.5(SNRPA):c.690-12_690-7del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,546,968 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: SNRPA NM_004596.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.688

Genes affected

SNRPA (HGNC:11151): (small nuclear ribonucleoprotein polypeptide A) The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5' splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-40764993-GTCGTTC-G is Benign according to our data. Variant chr19-40764993-GTCGTTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3037916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRPA	NM_004596.5	c.690-12_690-7del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000243563.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPA	ENST00000243563.8	c.690-12_690-7del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004596.5	P1
SNRPA	ENST00000601393.1	c.627-12_627-7del		splice_polypyrimidine_tract_variant, intron_variant		3
SNRPA	ENST00000601545.5	c.540-12_540-7del		splice_polypyrimidine_tract_variant, intron_variant		5
SNRPA	ENST00000596860.1	n.136-12_136-7del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152216 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00535

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000502 AC: 99 AN: 197204 Hom.: 0 AF XY: 0.000376 AC XY: 40 AN XY: 106438

Gnomad AFR exome AF: 0.00661

Gnomad AMR exome AF: 0.000212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000160 AC: 223 AN: 1394634 Hom.: 0 AF XY: 0.000139 AC XY: 96 AN XY: 689850

Gnomad4 AFR exome AF: 0.00642

Gnomad4 AMR exome AF: 0.000326

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000263

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.26e-7

Gnomad4 OTH exome AF: 0.000191

GnomAD4 genome AF: 0.00150 AC: 229 AN: 152334 Hom.: 1 Cov.: 32 AF XY: 0.00138 AC XY: 103 AN XY: 74488

Gnomad4 AFR AF: 0.00534

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000825 Hom.: 0

Bravo AF: 0.00180

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SNRPA-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 30, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs565642567; hg19: chr19-41270898;